THE SPINAL-CORD AS A SITE OF OPIOID EFFECTS ON GASTROINTESTINAL TRANSIT IN THE MOUSE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (1) , 22-27
Abstract
Intrathecal (i.t.) administration of morphine (1, 3 or 10 .mu.g) effectively inhibited the passage of a radiolabeled marker through the gastrointestinal tract of mice. This effect was reversed by pretreatment with naloxone (2 mg/kg s.c.). Transection of the spinal cord at the level of the 2nd thoracic vertebra (T2) slowed control transit when measured after 4 h, i.t. morphine inhibited transit in these paralyzed animals. Intracerebroventicular (i.c.v.) administration of morphine (1, 3 or 10 .mu.g) inhibited transit regardless of whether the spinal cord was transected at T2. Lower efficacy was seen with i.p. (10-300 .mu.g/kg) or i.v. (10 .mu.g) morphine than with comparable doses given i.t. (10 .mu.g). Administration (1, 3 or 10 .mu.g i.t.) of the proposed selective .delta. opioid agonist peptides, D-Ala2-D-Leu5-enkephalin, D-Pen2-L-Cys5-enkephalin or i.t. administration of D-Ser2-Leu-enkephalin-(Thr6) (10 .mu.g) were effective in inhibiting gastrointestinal transit. The proposed .kappa. agonists, ketocyclazocine (1, 3, or 10 .mu.g) or dynorphin-(1-13) (1, 10 or 100 .mu.g), did not affect transit after i.t. administration. Dynorphin-(1-13) (10, 30 or 100 .mu.g) or dynorphin-(1-9) (10, 30 or 100 .mu.g) did not affect transit after i.c.v. administration. While D-Ala2-D-Leu5-enkephalin (1, 3 or 10 .mu.g) and D-Ser2-Leu-enkephalin-(Thr6) (10 .mu.g) were efficacious in inhibiting transit by the i.c.v. route, the more .delta. selective D-Pen2-L-Cys5-enkephalin (1, 3, 10 or 20 .mu.g) was not.D-Pen2-L-Cys5-enkephalin (3, 10, or 20 .mu.g i.c.v.) was effective in producing analgesia (52.degree. C hot-plate test). Evidently, the spinal cord is a discrete and independent site of opioid effects on gastrointestinal motility. Opioids that are effective at 1 site are not always effective at the other. .delta.-Opioid receptors in the brain may mediate analgesia, but not gastrointestinal effects, and the effects on gut transit initiated by i.t. opioids are probably mediated by .mu. and .delta., but not .kappa., opioid receptors.